Lyrica and zoloft (A comparative blog) 

In this blog post, we are going to talk about the possible interactions between lyrica and zoloft. We will also compare the use of these two drugs as sometimes, they can be used for the treatment of similar diseases and are often prescribed together. 

Is there any interaction between lyrica and zoloft? 

A few studies suggest that lyrica and zoloft, when used together, may cause sodium deficiency. This interaction does not hold much clinical importance. These two drugs are often prescribed together for the treatment of depression and anxiety in epileptic patients.

Both lyrica and zoloft are also used for the treatment of generalised anxiety disorder (GAD). A 2014 study concluded that lyrica can provide relief from the symptoms associated with GAD, including insomnia and gastrointestinal side effects like nausea, vomiting and diarrhoea. 

Zoloft is also used off-label for the treatment of GAD. One study indicated the beneficial effects of lyrica in the treatment of fibromyalgia in patients taking antidepressants. 

It clearly indicates that taking these two medications together is safe and is, in fact, clinically significant in so many conditions. Researchers, right now as we speak, are trying to find the effects of lyrica in depressed patients. 

Certain epileptic patients show signs of depression and anxiety which was reduced by the use of lyrica. Some researchers suggest that the depression was induced by the condition of epilepsy, which is why the drug helped reduce those symptoms. 

Some researchers, on the contrary, believe that lyrica does possess a relationship with depression symptoms. This topic is under investigation and experts are trying to find any existing connection between the two. 

How do lyrica and zoloft work? 

Lyrica, brand name for Pregabalin, is an Antiepileptic drug. It is used to tone down the frequency of epileptic seizures or convulsions. The exact mechanism through which it produces its effects is not fully known, but it can decrease the excessive neuronal firing which results in seizures. 

Experts believe that it can bind to alpha2 subunits of calcium channels and decrease the release of certain excitatory neurotransmitters. 

Zoloft, on the other hand, is the brand name for sertraline. It is an antidepressant which blocks serotonin transporters (SERT) and inhibits the reuptake of serotonin. 

This results in an increased amount of active serotonin to bind to its receptors. It is an excitatory neurotransmitter which is responsible for modulating mood, cognition, reward, learning, memory, and various other psychological processes. 

If we look closely, both of these drugs have opposite mechanisms of action. One is responsible for increasing the amounts of excitatory neurotransmitters in your brain, while the other one works in the opposite way and decreases the availability of such neurotransmitters. 

It is extremely important to make sure if the concomitant use is absolutely required and there’s no other way around, because it is not recommended to use medications in combination when you can benefit from a single agent. 

Side effects of lyrica and zoloft 

There’s no such medication that does not come with side effects. These two, being no exception, also possess some adverse effects. 


Common side effects of lyrica include:

  • Xerostomia or dry mouth 
  • Weight gain 
  • Dizziness 
  • Somnolence
  • Swollen hands and feet
  • Headache
  • Vision problems 
  • Cloudy mind
  • Fatigue
  • Confusion
  • Joint pain 
  • Difficulty in remembering things
  • Abdominal pain 
  • Muscle twitching 

Lyrica can cause some serious side effects. These include:

  • Suicidal behavior 
  • Impaired motor coordination 
  • Thrombocytopenia or decreased levels of platelets
  • Water retention
  • Rhabdomyolysis, a condition associated with abnormal breakdown of muscles
  • Hypersensitive allergic reaction which may cause difficulty in breathing, tightening of chest skin rash, redness, blisters, etc. 


Common side effects of Zoloft include:

  • Loss of appetite
  • Tiredness
  • Feeling angry or agitated
  • Weight gain
  • Inability to digest food
  • Nausea
  • Diarrhoea
  • Loss of libido
  • Sweating/Night sweats
  • Tremors or shaking
  • Insomnia
  • Decreased sex drive
  • Muscle twitching 
  • Inability to ejaculate

Zoloft, sometimes, causes serious side effects. Consult your healthcare provider as soon as you can if these symptoms occur:

  • Seizure/convulsions
  • Suicidal behavior, especially in users younger tham 24 years of age. 
  • Eye pain with vision problems
  • Headache
  • Confusion
  • Agitation
  • Memory problems/Dementia 
  • Severe weakness and inability to move

Now, as you can clearly see, there are several side effects that are similar, including weight gain, dizziness, sleepiness, muscle twitching, fatigue etc. We can also clearly see some of the serious side effects being similar, including suicidal behavior, confusion, vision problems etc.

This clearly indicates that the use of these two agents together can cause something known as synergistic side effects. The concomitant use can highly increase the incidence of suicidal attempts in younger population. 

Make sure these two meds are used together only when your doctor has advised it. Using two medications together which affect your brain is not something ideal and should not be encouraged unless it is absolutely necessary to do so. 

Make sure you discuss everything in detail with your healthcare provider and ask if you’re at the best possible doses if you’re using these two together. 

Ensure proper use of medicines

  • Do not suggest medications, unless you are a healthcare professional yourself. Do not share medications. You might think your conditions match but oftentimes they don’t. It’s actually pretty dangerous.
  • If you fail to understand how to use the two drugs properly or have any question, ask your doctor or pharmacist.
  • Both of these drugs can pass into the breastmilk. Ask your doctor if you are a nursing mother. 
  • Ask your doctor before using lyrica and zoloft together if you’re pregnant or trying to conceive. 
  • Inform your healthcare provider of your medical history of any disease like hypertension, diabetes, asthma, COPD, autoimmune diseases etc. 
  • Avoid alcohol with the concomitant use of lyrica and zoloft. 
  • In case of overdose, immediately reach out to the hospital. Make sure you properly guide them about how much drug you have taken and when. 
  • If you experience unusual side effects, immediately contact your healthcare provider.
  • These drugs tend to induce suicidal behavior. If you have someone who shows suicidal behavior or you see hopelessness in them, make sure you keep an eye on them and get medical attention as soon as you can. 

Drug interactions of lyrica

It is important to rule out possible drug interactions between your medications. Lyrica can interact with the following drugs:

Narcotic analgesics 

Both narcotic opioid analgesics and lyrica decrease the amount of excitatory neurotransmitters in your brain. This can slow down your physiological functions including breathing rate. 

The concomitant use can cause severe respiratory depression, which could become deadly for people who already suffer from respiratory illnesses like asthma or chronic obstructive pulmonary disease (COPD). 

Make sure you ask your doctor if it’s necessary to use narcotic analgesics. Avoid substance abuse or you’ll end up messing your brain up. 


Alcohol can also act as a central nervous system (CNS) depressant. The synergistic effects of alcohol and lyrica can cause severe depression and suicidal behavior. 

Few studies suggest that combining lyrica with other agents which decrease the amounts of brain chemicals can result in paralysis or muscle wastage. If you’re a chronic alcohol user, cut back as much as you can. 

Antidiabetic agents

Certain diabetic agents may react with lyrica and cause increased water retention, which results in swelling or edema in upper and lower extremities, or any other part of the body. 

The concomitant use may cause weight gain and other disturbances. If you’re diabetic, make sure you use these two agents only if approved by your healthcare provider. 

There’s no known interaction between lyrica with any type of food. If you observe that your side effects get worse when you eat certain kinds of food, immediately reach out to your healthcare provider and avoid eating anything that triggers a negative reaction. 

Drug interactions of zoloft 

Following are the possible drug interactions of zoloft:

Monoaminoxidase inhibitors 

Do not use zoloft with any irreversible monoamine oxidase inhibitors (MAOIs). Concomitant treatment is highly contraindicated due to the risk of serotonin syndrome with symptoms like agitation, tremor and hyperthermia. 

Zoloft must not be initiated for at least 14 days after discontinuation of treatment with an irreversible MAOI. Zoloft must be discontinued for at least 7 days before starting treatment with an irreversible MAOI.


Do not use zoloft with pimozide. Combining these medications can increase the plasma concentration(availability of a drug in the blood) of pimozide to much higher levels. It can result in life-threatening arrhythmia.

Blood thinners 

Zoloft, if used concomitantly with non-steroidal anti-inflammatory drugs (NSAIDS), aspirin, anticoagulants like warfarin etc, can cause prolonged bleeding

Too much caffeine 

It is safe to drink coffee while you’re on zoloft but make sure you don’t drink too much of it. Coffee and zoloft both share some side effects. Concomitant use of zoloft and high amounts of caffeine can cause many pronounced and dangerous side effects. 


Concomitant use of zoloft and alcohol may cause much more pronounced symptoms of depression and anxiety


In this blog, we talked about the use of lyrica and zoloft together. These drugs can cause a number of side effects, but they are still prescribed together for a number of conditions. 

Lyrica decreases the amount of excitatory neurotransmitters in your brain, whereas zoloft is used to increase the quantity of active serotonin. Make sure you use these two meds together only if prescribed by your healthcare provider. 

FAQs: Lyrica and zoloft

What drugs should not be taken with Zoloft?

You should not take following medications with zoloft:

  • Monoaminoxidase inhibitors. The concomitant use increases the risk of serotonin syndrome. 
  • Tryptophan rich foods. 
  • Non-steroidal anti-inflammatory drugs (NSAIDS). The combination can increase the risk of bleeding 
  • Pimozide 

Can you take gabapentin with Zoloft?

Yes, you can use Gabapentin with zoloft, only if prescribed by your doctor. 

Which is best for anxiety, sertraline or pregabalin?

Sertraline and pregabalin both can be used for the treatment of anxiety and both produce satisfactory results. Your doctor will decide what medication is a safer option for you. 

Is pregabalin good for anxiety?

Yes, pregabalin has been shown to provide a good therapeutic response against anxiety. 

What painkillers can I take with sertraline?

Paracetamol is safe to use with sertraline. Ask your doctor before taking any other pain killer like diclofenac or naproxen, as these agents can increase the risk of bleeding in patients taking sertraline. 

Why should you not take sertraline at night?

If sertraline causes insomnia, loss of libido or urinary problems, it is not recommended to take it at night. Taking it in the morning can help avoid the complications associated with these side effects. 


  • I I Bondarenko et al. Zh Nevrol Psikhiatr Im S S Korsakova. (2012) – Use of pregabalin and sertraline in complex treatment of patients with partial epilepsy comorbid with depressive and anxiety disorders 
  • M Cvjetkovic-Bosnjak et al. Eur Rev Med Pharmacol Sci. (2015) – Pregabalin versus sertraline in generalised anxiety disorder. An open label study
  • James E Frampton. CNS Drugs. (2014) – Pregabalin: a review of its use in adults with generalized anxiety disorder
  • Lesley M Arnold et al. J Rheumatol. (2015) – Efficacy and Safety of Pregabalin in Patients with Fibromyalgia and Comorbid Depression Taking Concurrent Antidepressant Medication: A Randomized, Placebo-controlled Study 

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